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Biomedical subjects

J A Carlson

Publications and source records attributed to J A Carlson.

At least 91 records · Page 5Linked to original sources
PubMed1989

Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice.

Circulating alpha 1-antitrypsin is synthesized primarily in the liver and secreted into the bloodstream, where it serves as the major protease inhibitor. The PiZ variant of alpha 1-antitrypsin is associated with decreased levels of the protein in sera as a result of its retention within hepatocytes. Homozygosity for the variant allele predisposes individuals to the development of pulmonary emphysema and an increased risk for liver disease. We and others have previously demonstrated that the normal PiM human alpha 1-antitrypsin gene can be properly expressed in the livers of transgenic mice. The PiZ variant of the human alpha 1-antitrypsin gene was introduced into the germline of mice to determine whether the mutant protein would accumulate in mouse hepatocytes and if such accumulation would result in the development of liver damage in an animal model. As expected, the mutant human protein was abundantly synthesized in the livers of the transgenic animals and accumulated within the rough endoplasmic reticulum of hepatocytes as it does in human patients. PiZ mice developed significantly more liver necrosis and inflammation than PiM transgenic mice or control littermates. The degree of liver damage was correlated with the amount of PiZ alpha 1-antitrypsin accumulated in the liver of the different pedigrees of mice. Although 40% of PiZ mice tested were seropositive for mouse hepatitis virus (MHV), the degree of liver damage was not influenced by the MHV seropositivity; rather, it was related only to the presence of accumulated PiZ protein.

Animals↗
PubMed1988

Glomerular localization of circulating single-stranded DNA in mice. Dependence on the molecular weight of DNA.

Although it has been observed that DNA has a high binding affinity for the glomerular basement membrane (GBM) in vitro, glomerular localization of DNA has not been demonstrated in vivo. To evaluate this possibility, after injection of 125I ssDNA of varying molecular weight (mol. wt.) to normal mice, we measured glomerular levels of DNA in vivo. Following administration of 2 mg of 125I high mol. wt. purified single stranded(ss) DNA (2-6 kilobases; 0.7-2.0 x 10(6)D) to normal mice, DNA was not detected in glomeruli, despite measurable blood levels of DNA for 72 h. In contrast, after injection of 280 micrograms of low mol. wt. 125ssDNA (160-200 bases; mol. wt. = 5.3-6.6 x 10(4)D) to normal mice, glomerular localization was observed throughout the 24-h study period despite relatively low 125IssDNA blood levels. The results of these studies indicate that free circulating DNA can bind to sites within glomeruli in vivo, and that the size of DNA is crucial for this interaction. Since low mol. wt. DNA is present in the plasma of patients with active lupus, these findings raise the possibility that DNA may bind to glomeruli and serve as a planted antigen for in situ immune complex formation with circulating anti-DNA antibodies.

Animals↗
PubMed1988

Postoperative care of the gynecology patient.

This chapter has dealt with some of the general issues that impact upon postoperative care. Within the context of this volume, a detailed analysis of each subject is not feasible. Some subjects were deliberately deferred to other contributors. My intent was to review some basic physiology and patho-physiology to emphasize the complex physical and metabolic alterations produced by abdominal pelvic surgery and to emphasize my personal belief that an uncomplicated postoperative recuperation begins with appropriate presurgical care.

Enterocolitis, Pseudomembranous↗
PubMed1988

Tumor recurrence versus fibrosis in the female pelvis: differentiation with MR imaging at 1.5 T.

Twenty-two women with previous malignancies of the pelvis were examined with magnetic resonance (MR) imaging. In 21 of 22 patients, the MR imaging findings were confirmed with laparotomy on transvaginal biopsy. Twelve of the 22 patients had recurrent tumors; ten had a localized fibrotic mass, and two were found to have coexistent local fibrotic masses and distant recurrence. In 11 of the 12 patients with recurrence, MR imaging demonstrated the recurrent tumor as an area of increased signal intensity on long repetition time, long echo time spin-echo pulse sequences. Signal intensity of localized fibrosis varied with the time since initial treatment. Separate signal intensity measurements for T1- and T2-weighted images were obtained in regions of interest in recurrent tumors, early fibrosis (1-6 months after first treatment), and late fibrosis (more than 12 months). Ratios of signal intensity of muscle to that of fat were calculated, and a statistical analysis (Student t test) was performed. On heavily T2-weighted pulse sequences, the differences in signal intensity between late fibrosis and recurrent tumors were statistically significant (P less than .001). MR imaging is useful in identifying recurrent pelvic neoplasm and distinguishing it from posttreatment fibrosis.

Adult↗
PubMed1988

Multiple tissues express alpha 1-antitrypsin in transgenic mice and man.

Hepatocytes are considered to be the predominant source of alpha 1-antitrypsin (AAT), the major antiprotease in human plasma. The development of emphysema in the hereditary PiZ AAT deficiency state suggests that inhibition of leukocyte elastase in the lung is a major function of this protein. In addition, patients with AAT deficiency are at increased risk for developing cholestasis in infancy and chronic liver disease as adults. The mechanism for hepatic cell injury, however, is not understood. Transgenic mice that express the normal human AAT gene demonstrate abundant AAT in hepatocytes and specific cell types of numerous nonhepatic tissues. Immunoperoxidase techniques have previously disclosed AAT in many of the cell types seen in transgenic mice; however, the issue of local synthesis vs. endocytosis in these cell types has remained unresolved. In this study, AAT mRNA was seen in a variety of tissues in the transgenic mouse. Immunoelectron microscopy of renal tubular and small intestinal epithelial cells in the transgenic mice demonstrated AAT within the cisternae of the rough endoplasmic reticulum, as in hepatocytes. These findings support the possibility of local synthesis in the various cell types. The results suggest that in addition to maintaining tissue integrity in the lung, the protease/antiprotease balance may have physiological functions in other organs as well.

Animals↗
PubMed1988

Serine proteinase inhibitors as acute phase reactants in liver disease.

alpha 1-Antitrypsin, alpha 1-antichymotrypsin and angiotensinogen are three genetically homologous acute phase reactants which belong to the super family of serine proteinase inhibitors (serpins). In this report the dissociate expression of these respective genes in various liver diseases or after exposure to estrogen is emphasized. In addition, the influence of abnormal genetic variants on plasma levels of these proteins and on liver cell function is discussed.

Acute-Phase Proteins↗
PubMed1987

A severe outbreak of Escherichia coli O157:H7--associated hemorrhagic colitis in a nursing home.

In September 1985, an outbreak of Escherichia coli O157:H7 enteritis affected 55 of 169 residents and 18 of 137 staff members at a nursing home. The outbreak was characterized by two phases: a primary wave whose source was probably a contaminated sandwich meal and a secondary wave compatible with person-to-person transmission of infection. Among the elderly residents, the incubation period was 4 to 9 days (mean, 5.7 +/- 1.2). Older age and previous gastrectomy increased the risk of acquiring the infection (P = 0.01 and 0.03, respectively). Antibiotic therapy during exposure was associated with acquiring a secondary infection (P = 0.001). Hemolytic uremic syndrome developed in 12 affected residents (22 percent), 11 of whom died. Overall, 19 (35 percent) of the affected residents died, 17 (31 percent) from causes attributable to their infection. Antibiotic therapy after the onset of symptoms was associated with a higher case fatality rate in the more severe cases, possibly because patients with more severe disease tended to be treated with antibiotics. There were no complications or deaths among the affected members of the staff. Evidence of infection by verotoxin-producing E. coli O157:H7 was detected in 30 of 70 cases on the basis of isolation of this organism or demonstration of free verotoxin in stools. All isolates belonged to the same phage type. The high morbidity and mortality associated with this condition emphasize the need for proper food hygiene, rapid identification of outbreaks of disease, and prompt institution of infection-control techniques among the institutionalized elderly.

Adolescent↗
PubMed1987

Tissue specific expression of the human alpha-1-antitrypsin gene in transgenic mice.

Normal and mutant human alpha-1-antitrypsin genes were cloned from a PiMZ heterozygous individual. Nucleotide sequence comparison demonstrated a T to C transition in exon III and an G to A transition in exon V of the PiZ gene. A 14.4 kb DNA fragment containing the entire PiM gene plus 2 kb of 5' and 3' flanking genomic DNA sequences was introduced into the germ line of mice and five F0 transgenic lines were established. Transgenic F1 progeny from F0 parents exhibited high levels of human alpha-1-antitrypsin protein in their plasma. The human gene was expressed primarily in liver of the transgenic mice as it is in man. However, expression of the human alpha-1-antitrypsin gene was also observed in kidneys of the transgenic mice, which led to the observation that the endogenous mouse gene is also expressed in the kidney. These data indicate that cis-acting elements within or proximal to the human alpha-1-antitrypsin gene are able to direct its in vivo transcription with a high degree of tissue specificity.

Animals↗
PubMed1985

Hexamethylmelamine, methotrexate and 5-fluorouracil (HMF) for progressive ovarian carcinoma during therapy with cis-platinum, cyclophosphamide +/- doxorubicin.

Hexamethylmelamine, methotrexate, and 5-fluorouracil (HMF) is a second-line chemotherapy for patients with ovarian carcinoma refractory to platinum-based regimens. Two of 15 patients with tumor progression treated with HMF alone had objective complete responses while one had a 12-month disease-free interval (DFI). Among 8 patients treated with HMF and either intraperitoneal chromic phosphate and/or alternating platinum-based chemotherapy following second-look surgery which documented persistent carcinoma, 3 have experienced disease-free intervals of 19, 27, and 42 months. However, no one has been cured or had a long-term remission after HMF therapy alone.

Adult↗
PubMed1985

Nutritional assessment in gynecology patients.

A nutritional assessment was performed upon 72 patients admitted for major elective gynecologic surgery for nonmalignant diseases. This nutritional assessment included body weight, triceps skinfold, arm muscle circumference, creatinine-height index, serum albumin and transferrin, total lymphocyte count, and dermal antigen testing. We found that 29 patients (42%) had at least one test result indicating a nutritional deficiency. Of the 72 patients, 19 (26%) experienced a postoperative complication. The occurrence of a complication did not correlate with any nutritional parameter other than albumin (p = 0.013), but even then, the positive predictive value of albumin was only 40%. Age also correlated with complication status (p = 0.002).

Body Height↗
PubMed1984

Methyl-CCNU, doxorubicin, and cis-diamminedichloroplatinum II in the management of recurrent and metastatic squamous carcinoma of the cervix.

Twenty-three patients with recurrent unresectable carcinoma of the cervix or distant metastasis at initial presentation were treated with methyl-CCNU (175 mg/m2) and doxorubicin (45 mg/m2) on day 1 and cis- diamminedichloroplatinum II (90 mg/m2) on day 22 of a 42-day treatment cycle. Twenty-two patients had squamous carcinoma and 1 had adenosquamous carcinoma. There were two complete responses (CR), five partial responses (PR) (greater than 50% tumor reduction, greater than 3-month duration), four patients with stable disease (less than 50% reduction, greater than 3-month duration), and 12 patients who had tumor progression. One CR has been maintained greater than 28 months, and the other greater than 8 months. Total CR and PR was 7 of 23 (30.4%). Three 23 responses occurred among 15 patients (20%) who had cancer primarily confined to the pelvis, while 4 of 8 patients (50%) with distant metastasis responded. During the initial 2 cycles of chemotherapy, 12 patients had myelosuppression, defined as a leukocytes less than 3000/mm3, granulocytes less than 1,000/mm3, or platelets less than 100,000/mm3. There were no treatment-related deaths.

Adult↗
PubMed1984

Tamoxifen and endometrial carcinoma: alterations in estrogen and progesterone receptors in untreated patients and combination hormonal therapy in advanced neoplasia.

Estrogen receptors and progesterone receptors were measured in tumors from patients with previously untreated endometrial carcinoma before and after a 5-day course of tamoxifen citrate. On initial biopsy, 13 of 25 tumors (52%) were progesterone receptor-positive, whereas 21 of 25 tumors (84%) were progesterone receptor-positive after tamoxifen. Grades 1 and 2 tumors were more likely to demonstrate this increased incidence of measurable progesterone receptors. Considering these results, and the work of others who have shown that progesterone receptor-positive metastatic endometrial cancer is more responsive to progestin therapy than are progesterone receptor-negative tumors, we instituted a phase II clinical trial of tamoxifen plus progestin for patients with recurrent endometrial carcinoma. Thus far, however, the 33% total response rate achieved with the combination therapy has not been superior to standard progestin therapy.

Adenocarcinoma↗
PubMed1984

Platinum tissue concentrations following intra-arterial and intravenous cis-diamminedichloroplatinum II in New Zealand white rabbits.

Intra-arterial chemotherapy is supported by the rationale that regional infusion more than systemic administration can produce higher regional concentrations of cytotoxic drugs, thereby enhancing tumor kill. The hypothesis that intra-arterial infusion of cis-diamminedichloroplatinum II (DDP) enhances regional drug concentrations in tissue has not been studied. Therefore, 30 New Zealand white rabbits were treated with DDP. Fifteen animals were given DDP intravenously, and the other 15 received DDP by intra-arterial infusion into the terminal aorta. Necropsy was performed at 2, 6, 24, and 48 hours after infusion. Samples of tissue were analyzed for platinum content by flameless atomic absorption spectrophotometry. Uterine and ovarian platinum content was significantly greater after intra-arterial infusion than after intravenous infusion (P less than 0.001 and P less than 0.01, respectively). This substantiates the rationale that regional arterial infusion of DDP can achieve higher tissue platinum levels than the intravenous route, at least, in this animal model.

Animals↗
PubMed1984

Endoarterial pulmonary metastasis of malignant trophoblast associated with a term intrauterine pregnancy.

A previously healthy gravida 4, para 3, developed preclampsia and progressive dyspnea at the 37th gestational week and had bilateral pulmonary infiltrates on chest roentgenogram. She delivered a healthy, term, male infant with a normal appearing placenta. Postpartum, her respiratory status gradually worsened. A lung biopsy on the 20th postpartum day revealed intravascular trophoblasts, diffuse arteriolar thrombosis with pulmonary infarction, and subacute interstitial pneumonitis. Combination chemotherapy was instituted, but the patient died from respiratory insufficiency.

Adult↗
PubMed1984

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Acute Disease↗